DE69427526T2 - APPLICATOR FOR TRANSCUTANEOUS ADMINISTRATION OF A MEDICINE - Google Patents

Abstract

A transcutaneous iontophoretic drug applicator, which includes an array of reservoirs which are electrically insulated from one another, some of which contain the drug to be administered. The applicator further includes a partially electrically conducting layer, preferably formed of two portions, each segments corresponding to an electrode, which overlies and contacts the reservoirs, and electrodes which overly and contact the partially electrically conducting layer. An electrical power source supplies power to the electrodes and causes the drug to be pushed out of the reservoirs and into the skin. The applicator is designed to keep the local current flux below threshold irritation and burn levels regardless of variations in electrical skin resistance.

Description

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to transcutaneous or transdermal drug delivery systems, an applicator for use in the transcutaneous delivery of drugs.

A variety of methods are used to deliver various medications to patients. For example, many drugs are taken orally. The medications taken this way are absorbed through the blood system in the stomach and intestines and distributed throughout the body.

Another delivery method involves introducing the medication directly into the bloodstream by injection into a vein of the patient. Such delivery may be accomplished using a hypodermic syringe for essentially instantaneous delivery of the drug dose, or a more uniform and prolonged delivery may be achieved using extended intravenous lines.

A third delivery method that is gaining widespread acceptance involves transcutaneous drug delivery, ie the delivery of the drug into the patient through the skin. In certain circumstances, transcutaneous drug delivery offers advantages in particular in that it allows for the continuous and metered delivery of medications to the body without the complications and inconveniences of intravenous administration.

Such a measured delivery of medication over a relatively long period of time is particularly desirable for the delivery of medications that can be harmful if given in large doses and for medications such as various types of painkillers that are most effective when delivered continuously.

A number of transcutaneous drug delivery systems are known. Perhaps the simplest of these involves placing the drug in contact with the skin and allowing the drug to permeate through the skin by osmosis and/or related spontaneous mass transport phenomena. This technique is commonly used, for example, to administer nitroglycerin. A more sophisticated transcutaneous drug delivery technique, known as iontophoresis, uses electrical energy to actively cause the drug to permeate the skin and allows better control of the rate of drug delivery and the depth of penetration.

Reduced to its bare essentials, iontophoresis involves the application of an electromotive force to propel ionic chemicals, typically drugs, through the skin so that they can be absorbed by the underlying tissues and nearby blood vessels.

An iontophoretic device comprises two electrodes. One of the electrodes has in its vicinity the ion species that is to be driven through the skin. The other electrode, in close proximity to the first electrode, serves to complete the electrical circuit through the body. In use, both electrodes are placed in contact with the skin. An electromotive force is applied to the electrodes, which creates an electrical circuit between the two electrodes, which passes through the skin and underlying tissues, and which drives the species of ionic drug away from the first electrode and through the skin.

EP-A-0 337 642 describes a transcutaneous iontophoretic device comprising an insulating member having an array of reservoirs containing a drug and electrodes adhered to the surface of the insulating member and electrically connected to an electrical source.

Iontophoretic transcutaneous drug delivery as currently performed is not without problems. A major component among these is the difficulty in ensuring a relatively uniform low electrical flux between the two electrodes.

It has been widely recognized that the difficulty in maintaining an appropriate electrical flow stems from the difficulty of establishing and maintaining good contact between the device and the skin. The skin is normally a rough surface and even when all hair has been shaved from the area to which the electrodes are to be applied, the remaining surface remains three-dimensional and contains various imperfections and inhomogeneities, such as clipped hairs, follicles, cuts, scar tissue and the like, which preclude the establishment of good electrical contact between the applicator and the skin.

Various conductive gels, with or without various flux-enhancing components, have been used to fill the space between the applicator and the skin to at least partially overcome some of the difficulties encountered when attempting to uniformly contact the essentially flat applicator and the microscopically highly three-dimensional surface of the skin.

Another way of ensuring better contact between the electrodes and the skin is described in U.S. Patent No. 4,708,716, and involves the use of an applicator having a plurality of electrodes that are elastically connected together so that the entire applicator is able to better bend and conform to better follow the rough contours of the skin surface on which the applicator is used.

This solution, while useful on a large scale in conforming the overall shape of the applicator to the shape of the skin surface, is ineffective in overcoming the difficulties caused by blemishes and inhomogeneities of the skin. Some of these features, e.g. cuts in the skin, present an electrical path which offers significantly lower electrical resistance than the surrounding skin. The reduced resistance causes the current to concentrate in and around the blemish and, if the local current flow increases sufficiently, it can cause undesirable consequences such as tingling, irritation and even burns. The phenomenon is further exacerbated by the fact that the initial concentration of the current causes a further drop in local resistance and a further increase in local current. This snowball effect serves to quickly form a "hot spot" which causes irritation and burns.

Various methods and procedures have been developed or proposed to eliminate such galvanic burns. The general goal is to keep the local current density, i.e. the current per unit area of skin, below the threshold at which it will burn or cause unacceptable irritation.

Current density uniformity can be improved by avoiding wrinkles, creases and other avoidable inhomogeneities between the applicator and the skin and by using different gel-moistened pads between the electrode and the skin. However, such techniques are ineffective in avoiding irritation and burns caused by the concentration of the electrical current as a result of unavoidable and often undetected imperfections in the skin, such as microscopic cuts or punctures.

One possible solution is to use an array of electrodes, each of which is connected in parallel to a current source through a certain resistance. Each resistance is of a type that is relatively large compared to the resistance normally involved in penetrating the skin. In this way, changes in the resistance of the skin surface cause a small effect on the current density.

Transcutaneous drug delivery systems typically use a current flow as low as 0.0001 amps per square centimeter of skin surface, while the electrical resistance of the skin to current flow is on the order of 6 to 9 K ohms. Thus, if a typical power source such as a 1.5 volt battery is used, the total system resistance per square centimeter of skin surface should be approximately 15 K ohms. A portion of this resistance is attributable to the battery resistance and the resistance of various other components of the applicator through which the current flows. The balance of the resistance, which is typically the sum total of the absolute resistances, is provided by some current limiting device, typically a resistor connected in series with each electrode in the electrical circuit.

If the skin resistance of a specific spot on the skin is significantly lower than if an open cut is involved, the local skin resistance drops significantly. However, since the skin resistance only accounts for a small proportion of the total local resistance, the total local current only increases slightly and remains below the values that would cause irritation or burns.

The difficulty with such a configuration is that the device described therein is very difficult to build and thus expensive. A related disadvantage is that such a device, made up of a large number of individual electrodes and resistors, could be unreliable and suffer from an unacceptably short storage time and operating time. Therefore, there is a widely recognized need for, and it would be very desirable to have, an iontophoretic transcutaneous drug applicator which would have the properties of effectively limiting the current flow introduced into the skin to safe levels and which at the same time would be inexpensive to manufacture and very durable and robust during storage and use.

SUMMARY OF THE INVENTION

According to the present invention there is provided a transcutaneous iontophoretic chemical applicator for delivering a chemical comprising an array of reservoirs electrically isolated from one another, at least one of the reservoirs containing the chemical, and a source of electrical current, characterized in that the applicator further comprises (a) a partially electrically conductive layer contacting and overlying at least two of the reservoirs, the partially electrically conductive layer allowing current to flow perpendicular to the partially electrically conductive layer but presenting substantially unlimited resistance to current flow parallel to the partially electrically conductive layer, and (b) electrodes physically and electrically contacting and partially overlying the conductive layer so that different portions of the current flowing between the electrodes flow through the partially conductive layer at different distances so as to serve to equalize the overall path resistance of the different portions of current; and in that the electrical power source is electrically connected to the electrodes.

According to further features of the preferred embodiment of the invention, which are described below, the electrodes include a single pair of electrodes.

According to still further features in the described preferred embodiments, the partially electrically conductive layer, which may be made of a semiconductor, is made of a single layer overlying all of the reservoirs.

According to still further features in the described preferred embodiments, the partially electrically conductive layer is made of two layers, each substantially overlying one half of the reservoirs.

The present invention successfully addresses the disadvantages of the currently known configuration by providing a transcutaneous drug applicator in a preferred embodiment which is made from an array of reservoirs, some of which contain the drug to be delivered, the reservoirs being overlaid by a single layer or by a pair of adjacent layers made of a material which is partially conductive and which serves to significantly increase the electrical resistance of the circuits through each of the reservoirs. The partially conductive layer or layers are in turn overlaid by one or two electrodes which serve to distribute the current uniformly across the reservoirs.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described herein by way of example only with reference to the accompanying drawings in which:

Figure 1 is a side cross-sectional view of an applicator according to the present invention;

Figure 1A is a perspective cross-sectional view of an applicator according to the present invention;

Fig. 2 is a perspective view of a reservoir assembly;

Figure 3 is an exploded perspective view of a reservoir assembly and a plurality of electrically conductive layers made from a single integral layer;

Fig. 3A is a perspective exploded view of a reservoir assembly and a partially electrically conductive layer made from two adjacent sections;

Fig. 4 is a perspective view of a reservoir assembly and partially electrically conductive layer of Fig. 3 as they appear when assembled together;

Fig. 4A is a perspective view of the reservoir assembly and a partially electrically conductive layer of Fig. 3 as they appear when assembled together; the partially electrically conductive layer being made from two adjacent sections;

Fig. 5 is an exploded perspective view of a reservoir assembly assembled with a partially electrically conductive layer and a pair of electrodes;

Fig. 5A is an exploded perspective view of a reservoir assembly assembled with a partially electrically conductive layer and a pair of electrodes, the partially electrically conductive layer being made from two adjacent sections;

Fig. 6 is a perspective view of the reservoir assembly, the partially electrically conductive layer and the electrodes of Fig. 5 as they appear when assembled together;

Fig. 6A is a perspective view of the reservoir assembly, electrically conductive layer and electrodes of Fig. 5A, as what they look like when joined together, with the partially electrically conductive layer being made from two adjacent sections;

Fig. 7 is a perspective view of the reservoir assembly, a partially electrically conductive layer of two sections, a pair of electrodes and an energy source in the form of a planar layer;

Figure 9 is a side cross-sectional view of an embodiment of an applicator according to the present invention having a removable seal;

Fig. 10 is a view of the applicator of Fig. 9 after removal of the removable seal;

Fig. 11 A shows a conventional circular applicator;

Fig. 11B shows a circular applicator according to the present invention;

Fig. 12A shows how the streamlines of the applicator according to Fig. 11A concentrate at the location of an inhomogeneity;

Fig. 12 B shows that the streamlines of the applicator according to Fig. 11B remain largely unchanged;

Fig. 13A shows how the streamlines of an applicator according to Fig. 11A concentrate at the location of a short circuit;

Fig. 13B shows that streamlines of an applicator according to Fig. 11B remain largely unaffected by a short circuit;

Fig. 14A shows that the voltage drop across an applicator according to Fig. 11A is constant when the applicator is correctly placed;

Fig. 14B shows that the voltage drop across an applicator according to Fig. 11 B is constant when the applicator is correctly placed;

Fig. 15A shows that the voltage drop across an applicator according to Fig. 11A is the same whether the applicator is correctly or incorrectly placed;

Fig. 15B shows that the voltage drop across an applicator according to Fig. 11B is very different when the applicator is misplaced than when the applicator is misplaced.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is a low cost but robust transcutaneous drug delivery applicator that has the ability to effectively limit the amount of current able to reach specific locations on the skin.

The principles and operation of an applicator according to the present invention can be better understood by reference to the drawings and the accompanying description.

Referring now to the drawings, Figures 1 and 1A illustrate in cross-section an embodiment of an applicator according to the present invention. The illustrated applicator is constructed from a number of components which are identified below and whose structures and function are described in more detail below.

In particular, the applicator includes a reservoir assembly 10 on its side closest to the skin 11 to which the device is to be applied. Directly above, and in contact therewith, is a reservoir assembly 10, a partially electrically conductive layer 12 which may be composed of a single layer, or alternatively which may be composed of two adjacent layers lying side by side as described hereinafter. While reference is made to a partially electrically conductive layer 12 in the singular throughout the specification and in the claims, it is intended that such terminology also include the case where the layer is composed of two or more segments which lie substantially in the same plane and which are approximately adjacent to one another, but preferably somewhat separated from one another. A pair of electrodes 14 is disposed directly above and in contact with the partially electrically conductive layer 12. Above the electrodes 14 is a battery assembly 16 or other suitable power source as described hereinafter, which are connected to one another and to electrodes 14 in a suitable manner as described hereinafter. Batteries 16 may be electrically insulated from electrodes 14 by an insulating layer 18 interposed between electrodes 14 and batteries 16. Batteries 16 and the entire assembly is enclosed in a suitable box or housing 20, which may also contain an activator or microprocessor 22 for controlling the operation of the applicator, and may further contain an activation button 24 and a bolus button 26, as will be described below.

Each of the above components will next be further described with reference to Fig. 1 and further with reference to Figs. 2 to 6, which form a series of perspective construction diagrams showing the shape and location of various key components of the applicator according to the present invention.

In Fig. 1 there is shown a view of a reservoir assembly 10 which forms the lowest components of the applicator according to the present invention, ie the component which comes into direct contact with the patient's skin 11 and which contains the medication to be administered to the patient.

A reservoir assembly 10 may be of any suitable length, width and height and may be made of any suitable material, preferably silicon, provided that the reservoirs are electrically isolated from each other, preferably, as shown in Figure 2, a reservoir assembly 10 is made of a single electrically isolated body formed with an array of preferably uniformly shaped volumes 30 integrally formed therein.

The square honeycomb structure shown in Figure 2 is purely illustrative. It should be noted that many other shapes of volumes 30 are possible, including, but not limited to, rectangular, hexagonal, or circular, and the like. It should also be noted that the dimensions of each of the volumes 30, as well as the overall dimensions of the reservoir assembly 10, can be varied as necessary to meet particular needs. It should similarly be noted that volumes 30 may alternatively be of irregular microscopic or smaller structures, such as the pore structure of a suitable insulating material.

The volumes 30 are filled with a suitable electrically conductive material, such as various electrically conductive gels. Some of the volumes 30 additionally contain suitable amounts of one or more drugs, which are typically in suspension or dissolved in the conductive gel. In the example of Figure 2, it is assumed for purposes of illustration that half of the volumes 30, i.e. 54 reservoirs closest to the viewer, contain drugs, while the other 54 do not.

The drugs contained in some of the volumes 30 are either in ionic form or will be ionized during the application of an electric field. The charge of the ionized drugs is the same as that of the volumes 30 in which they are located, causing the drug to be driven out of its volume 30 and into the skin 11 which lies directly beneath it.

The electrically conductive gel is typically sufficiently viscous to remain in volume 30 while the drug molecules find their way, under the influence of the electromotive force, through the gel and into the skin. Prior to use, the bottom portion of the reservoir assembly 10 may be covered with a disposable cover layer (not shown) which is removed prior to use of the applicator. Alternatively or additionally, the bottom-facing openings of the volumes 30 may be covered by microporous or semipermeable membranes which allow the drug molecules to exit the volumes 30 but prevent leakage of the conductive gel.

As best seen in Figs. 3 and 4, the partially electrically conductive layer 12 overlies at least two volumes 30 of the reservoir assembly 10, and is preferably laminated, deposited, painted or co-injected therewith. In one embodiment shown in Fig. 3, a single partially electrically conductive layer 12 overlies all of the volumes 30 of the reservoir 10. In a preferred embodiment shown in Figs. 3A and 4A, the partially electrically conductive layer 12 is constructed of two segments 12a and 12b which are slightly separated from each other, each of which overlies a portion, preferably substantially one half of the volumes 30, and which preferably substantially conform in their dimensions and coverage to the two electrodes described below. Dividing a partially electrically conductive layer 12 into two segments helps to further electrically separate the zones of influence of the two electrodes. A partially electrically conductive layer 12 or 12a and 12b may be made of any suitable material, such as electrically conductive polymers such as suitable vinyls or epoxies or carbon, charged or surface metallized plastics. Preferably, a partially electrically conductive layer 12 or 12a and 12b is made of a semiconductor material such as silicon containing carbon (graphite) particles.

The nature and thickness of partially electrically conductive layers 12 are such that current is able to flow through them in the vertical direction where the layer is relatively thin, but that essentially no current is able to flow transversely through the layer due to the large thicknesses involved. Thus, a partially electrically conductive layer 12 presents a certain appropriate selected resistance to current flow in the direction perpendicular to its major surfaces, but offers almost infinite resistance to current flow in the direction parallel to its major surfaces, thereby causing current to flow directly downward through the layer and preventing almost any current from flowing laterally. A partially electrically conductive layer 12 so acting presents an array of resistors of an appropriate resistance value in the vertical direction, but without the large expense and operational difficulties of separate discrete resistors and electrodes for each of the reservoirs.

As best seen in Figs. 5 and 6 and Figs. 5A and 6A, electrodes 14, which may be made of any suitable material including, but not limited to, aluminum or other metallic foils or conductive rubber or resin films, are disposed overlying, and preferably laminated to, partially electrically conductive layers 12 or 12a and 12b. A preferred embodiment is shown in Figs. 5 and 6 and 5A and 6A in which a single pair of electrodes 14 is used, each electrode covering approximately half of the active surface of the applicator, corresponding to approximately half of the reservoirs. In the configuration of Figs. 5A and 6A, the two portions of the partially electrically conductive layer 12a and 12b correspond substantially in their coverage to that of the electrode 14. However, it will be well understood that it is possible to use an array of pairs of electrodes, e.g. in which each element of each pair of electrodes overlies one or a small number of volumes 30.

Another embodiment is shown in Fig. 7 in which electrodes 14 extend to cover the entire surface of partially electrically conductive layers 12 or 12a and 12b. Such a configuration makes it easier for laminated or co-injected electrodes 14, which are preferably made of a suitable plastic impregnated with conductive components, such as graphite, to form a monolithic structure. A device according to the present invention further comprises a suitable electrical power source, preferably batteries 16 (Figs. 1 and 1A), which is electrically connected in a suitable manner (not shown) to electrodes 14. Preferably, the power source is an array of miniaturized batteries, e.g. those used in electrically powered clocks, connected in series. It will be understood that a variety of power sources, including any of a wide variety of possible batteries configured in a suitable manner, may be employed. For example, the power source may be in the form of an energy-delivering layer 116 that lies directly over the electrodes 14, as shown in Figure 8. An energy-delivering layer 116 may be made of a suitable plastic material, and may be laminated thereto or co-injected with the layer or layers it overlies.

Preferably, an applicator according to the present invention, particularly one as described in connection with the embodiment of Figure 8, is supplied in pre-packaged disposable units which are ready for application to the skin.

Preferably, as shown in Figure 9, each applicator is supplied packaged in a case made of two sections - an upper case 120, which is preferably permanently attached to the applicator, or may be an integral part thereof, and a removable seal 122 which seals the reservoir assembly 10 prior to use of the applicator.

Prior to use, an upper housing 120 and a removable seal 122 are bonded around their adjacent peripheries. Any suitable means may be used to make this bond. Immediately prior to use, the removable seal 122 is torn off and discarded, exposing the lower portions of the reservoir assembly 10 (Fig. 10) and the periphery of the upper housing 120. The newly exposed surfaces of the upper housing 120 are characterized by a suitable adhesive material which will assist in holding the applicator to the skin after the applicator has been pressed onto the skin. Preferably, the lowermost surfaces of the solid elements making up the reservoir assembly 10, e.g., the insulating walls, are also characterized by a suitable adhesive. The presence of adhesive at these points causes uniform contact between the reservoir series 10 and the user's skin.

The electrical connection between the power source and the electrodes 14 may be effected by various means, including, but not limited to, the use of electrical lead cables, metal foils and the like.

The upper portion of an applicator according to the present invention may be sealed by any conventional box or housing 20, including but not limited to a plastic cover or carrier. Box or housing 20 may also include an activator or similar means for turning the power source on and off in preferred embodiments of the present invention. In this regard, box or housing 20 is characterized by an activation button 24.

Box or housing 20 may further include a bolus button 26 which will allow a temporary increase in the rate of drug injection. Such increases are often desirable in the administration of pain medication where the patient desires to temporarily increase the dosage to accommodate unusually severe pain. It should be noted that because an applicator according to the present invention is designed to limit the local current density applied to the skin, a bolus delivery mechanism may well be used without fear of irritation or burns.

Preferably, an applicator according to the present invention further comprises a microprocessor 22 for controlling the rate of administration of the medication. A microprocessor 22 may be used to administer the medication based on one or more of predetermined programs which may be determined by the medication manufacturer, the physician and/or the patient to optimize medication delivery by maximizing the effectiveness of the medication and minimizing any adverse health effects.

While the embodiments described hereinbefore are based for illustrative purposes on a reservoir arrangement consisting of two adjacent substantially square or rectangular arrays of a medicine-containing set of volumes, it will be appreciated that many other geometries are possible.

For example, a device according to the present invention may be configured with one of the sets of volumes located centrally and surrounded by a second set of volumes forming an annulus around the first set. That is, the applicator could, for example, be circular with one electrode (i.e., the anode) and its associated medicine-containing volume located at or near the center of the circle, while the second electrode (i.e., the cathode) and its associated medicine-containing volumes form an annulus around the first electrode.

In Figs. 11 to 15, cross-sectional views of such circular applicators are shown as they would appear when applied to the patient's skin (not shown), with Figs. 11A, 12A, 13A, 14A and 15A showing prior art applicators, while Figs. 11B, 12B, 13B, 14B and 15B showing corresponding applicators according to the present invention.

A conventional circular applicator (Fig. 11A) includes a central electrode 300 and an annular electrode 302, each of which completely overlies a central common reservoir 304 and an annular common reservoir 306. Also shown in Fig. 11A are the locations within the patient's skin (not shown) of three representative electrical current lines 310, 312 and 314. Note that current line 310, which is closest to the applicator and which is the shortest of the current lines shown, will conduct more current than streamline 312, which is longer. Streamline 312 will in turn conduct more current than streamline 314, which is even longer. The relative amount of current conducted is schematically represented by the thickness of the streamlines.

The reason for the different current magnitudes is that current flowing through the longer current lines must cross more skin resistance than current flowing through the shorter paths. The consequences of such a current differential are therefore undesirable, resulting in an uneven distribution of the medication to the skin, with the shorter current lines carrying most of the medicine while the longer lines carry little or no medicine. In addition, the concentration of the current could lead to hot spots and the accompanying irritation or burns, as described in more detail below.

A circular applicator according to the present invention is shown in Fig. 11B. Here, a central electrode 400 and an annular electrode 402 partially overlie, respectively, a central partially electrically conductive layer 420 and an annular partially electrically conductive layer 422, which may be made of materials similar to those described in connection with the basic embodiments of Figs. 1 to 10. A central partially electrically conductive layer 420 and annular partially electrically conductive layer 422 in turn overlie, preferably completely, a centrally divided reservoir 404 and an annularly divided reservoir 406.

As described in connection with the embodiments of Figures 1 to 10, current passes from the electrodes through the partially conductive material, into the individual volumes of the reservoirs and into the skin. The relative size and dimensions of the electrodes 400 and 402 and the reservoirs 404 and 406 and their relative arrangement and the properties and dimensions of the partially conductive layers 420 and 422 are selected to reduce disparity in the total resistance of the various current paths so that substantially all paths of current between central electrode 400 and annular electrode 402 tend to be of substantially equal total sum resistance and therefore carry substantially equal currents as indicated by current lines 410, 412 and 414 which are visually represented with lines of equal thickness.

For example, in Fig. 11B, it will be seen that current following current line 414 passes from an annular electrode 402 directly through the thickness of an annular partially electrically conductive layer 422, through one of the volumes of an annular reservoir assembly 406, through the skin via current line 414, through one of the volumes of a central reservoir assembly 404, directly through the thickness of the central partially electrically conductive layer 420, and to the central electrode 400.

In contrast, current following current line 410 leaves the annular electrode 402 and must travel across an annular partially electrically conductive layer 422 from a position near its outer periphery to a position near its inner periphery, while at the same time the current must pass through the thickness of an annular partially electrically conductive layer 422. The current must then pass through one of the volumes of an annular reservoir assembly 406, through the skin via current line 410, through one of the volumes of the central reservoir assembly 404. The current must then traverse the thickness of a central partially electrically conductive layer 420 while also passing across it from a point near its outer periphery to a point near its center where a central electrode 400 is located.

The well-designed additional path through all partially conductive layers of all but the most penetrating current lines tends to equalize the total resistance of each current path and therefore causes a uniform distribution of current throughout the applicator, reducing or eliminating the possibility of hot spots and ensuring a uniform delivery of medicine to the patient.

Some of the consequences and advantages of a configuration such as that shown in Fig. 11B are illustrated in Figs. 12 to 15. In Fig. 12A, the occurrence of a hot spot is schematically illustrated when using a conventional applicator. When an inhomogeneity is encountered, the current lines tend to concentrate, forming a hot spot which could cause irritation or even burns. In contrast, an applicator according to the present invention, as shown in Fig. 12B, forms a uniform zone of low current density. When an inhomogeneity is encountered, only a small proportion of the current is able to concentrate.

Similarly, when a short circuit occurs in a conventional applicator (Fig. 13A), e.g. when a drop of sweat is introduced between the central and annular sections of the applicator, most of the current is concentrated and passes through the path of least resistance, i.e., through the short circuit. This is because it is the electrical resistance of the skin which is by far the most important contributor to the resistance to current flow in such systems.

In contrast, because in an applicator according to the present invention (Fig. 13B) the resistance offered by the partially conductive layers is a very significant proportion of the total resistance, a sudden drop in skin resistance lowers the total resistance to a much smaller degree and therefore the concentration of current is significantly lower.

Finally, an applicator according to the present invention (Figs. 14B and 15B), unlike prior art applicators (Figs. 14A and 15A), can be used to give accurate indications of its misplacement on the patient's skin.

In Figs. 14A and 14B the case is shown where both applicators are properly placed. As described above, the current field produced by an applicator according to the present invention will be much more uniform than that produced by a conventional applicator. When the total potential is measured across each well-placed applicator, the voltage loss will be the same.

Now assume that both applicators are incorrectly placed so that a portion of each applicator is not in good electrical contact with the skin. With a conventional applicator (Fig. 15A) there will be a concentration of current in those areas where electrical contact is good and the total voltage loss across the electrodes will be the same as if proper contact was maintained over the entire applicator surface.

In contrast, because the ability of the current to concentrate in an applicator according to the present invention is severely limited (Fig. 15B), the result of a false contact of a portion of the applicator will be a reduced overall voltage drop across the electrodes. Such a voltage drop will give the operator an immediate and accurate indication of incorrect placement of the applicator.

It should be noted that the scheme illustrated in the embodiment of Figures 11B to 15B can be used in geometries other than those involving a central electrode and a surrounding annular electrode. For example, the same scheme can be used in conjunction with the embodiments of Figures 1 to 10 by measuring and sizing the electrodes so as to cover only a small portion of the surface of the partially conductive layer or layers and by placing each of the electrodes near the edge of the applicator that is furthest from the other electrode.

It should also be noted that such a scheme as that described above can be employed by using such electrodes as those in the embodiments of Figures 1 to 10 which overlie all or most of the partially conducting layer or layers, but where other means are used to ensure that different portions of the current experience different resistances as they traverse the partially conducting layer or layers, e.g. by using a partially conducting layer or layers which have varying thicknesses and thus resistances for different current lines.

While the invention has been described in terms of a limited number of embodiments, it should be understood that many variations, modifications and other applications of the invention may be made.

Claims (16)

1. A transcutaneous iontophoretic chemical applicator for delivering a chemical, which comprises an array of reservoirs (10, 30; 404, 406) which are electrically isolated from one another, at least one of the reservoirs (10, 30; 404, 406) containing the chemical, and an electrical current source (16; 116), characterized in that the applicator further comprises: (a) a partially electrically conductive layer (12; 12a, 12b; 420, 422) overlying and contacting at least two of the reservoirs (10, 30; 404, 406), the partially electrically conductive layer (12; 12a, 12b; 420, 422) allowing current to flow perpendicular to the partially electrically conductive layer (12; 12a, 12b; 420, 422) but presenting a substantially infinite resistance to the flow of current parallel to the partially electrically conductive layer (12; 12a, 12b; 420, 422); and (b) electrodes (14; 400, 402) which physically and electrically contact and at least partially overlie the partially electrically conductive layer (12; 12a, 12b; 420, 422) so that different portions of the current flowing between the electrodes (14; 400, 402) flow through the partially electrically conductive layer (12; 12a, 12b; 420, 422) at different distances and thus tend to to balance the total path resistance of the different components of the current; and in that the electrical power source (16; 116) is electrically connected to the electrodes (14; 400, 402). 2. Applicator according to claim 1, wherein the electrodes (14; 400, 402) include a single positive electrode and a single negative electrode. 3. Applicator according to claim 1, wherein one of the electrodes (14; 400, 402) is an annular electrode (402) overlying an annular partially electrically conductive layer (422) surrounding a central electrode (400) overlying a central partially electrically conductive layer (402), the annular electrode (402) being arranged near the outer periphery of the annular partially electrically conductive layer (422). 4. Applicator according to one of the preceding claims, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) is of non-uniform thickness. 5. Applicator according to one of claims 1 to 2, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) is constructed from a single layer (12) overlying all of the reservoirs (10, 30). 6. Applicator according to claim 1 or 2, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) consists of at least two segments (12a, 12b; 420, 422), wherein each of the segments (12a, 12b; 420, 422) overlies some of the reservoirs. 7. Applicator according to one of the preceding claims, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) contains a semiconductive material. 8. Applicator according to claim 7, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) contains silicon and further contains carbon particles. 9. Applicator according to one of the preceding claims, wherein the reservoirs (10, 30; 404, 406) are a plurality of uniformly shaped volumes which are integrally formed from a layer of electrically insulating material. 10. Applicator according to claim 1, wherein the reservoirs (10, 30; 404, 406) are a plurality of microporous volumes integrally formed from a layer of electrically insulating material. 11. Applicator according to claim 9 or 10, wherein the electrically insulating material contains silicon. 12. Applicator according to one of the preceding claims, wherein the electrical power source (16; 116) is a layer power source (116). 13. Applicator according to one of the preceding claims, further comprising a removable seal (122) covering the array of reservoirs (10, 30; 404, 406) which is removed prior to use. 14. The applicator of claim 13, wherein removing the removable seal (122) exposes an adhesive. 15. Applicator according to claim 14, wherein the adhesive is disposed on the exposed surfaces of the array of reservoirs (10, 30; 404, 406). 16. Applicator according to claim 1, wherein the chemical is a drug, wherein the reservoirs (10, 30; 404, 406) are integrally formed in an electrically insulating layer, wherein the partially electrically conductive layer (12; 12a, 12b; 420, 422) is arranged above and in contact with the reservoirs (10, 30; 404, 406), and a pair of electrodes (14; 400, 402) is present.